CTLA4-Ig treatment prevents murine experimental autoimmune encephalomyelitis

Cross, Anne H.; Girard, Tanya; Giacoletto, K S; Evans, Robert J.; Karr, Robert W.

doi:10.1016/0165-5728(94)90286-0

Cited by 3 publications

(5 citation statements)

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“…This underscores the importance of the CD28/CTLA‐4 – CD80/CD86 pathway in regulating the induction of autoimmune diseases. CTLA‐4‐Ig is able to block the activation and expansion of pathogenic T cells in vitro (107) and is also effective in blocking autoimmune disease of the CNS, as in vivo administration prevents the development of EAE (111, 112). As CTLA‐4‐Ig binds to both CD80 and CD86 and completely blocks T cell costimulation through CD28, other studies have aimed at deciphering whether the two ligands have differential roles in regulating autoimmune responses.…”

Section: Ctla‐4mentioning

confidence: 99%

“…This underscores the importance of the CD28 ⁄ CTLA-4 -CD80 ⁄ CD86 pathway in regulating the induction of autoimmune diseases. CTLA-4-Ig is able to block the activation and expansion of pathogenic T cells in vitro (107) and is also effective in blocking autoimmune disease of the CNS, as in vivo administration prevents the development of EAE (111,112).…”

Section: Functional Role Of Ctla-4 and Its Ligands In Cns Autoimmunitymentioning

confidence: 99%

“…Both CTLA-4 and TIGIT have intrinsic inhibitory functions as blocking antibodies exacerbate EAE (106)(107)(108)141). Furthermore, like CTLA-4-Ig, soluble TIGIT can suppress autoimmune diseases when administered in vivo (111,112,141). Finally, both CTLA-4 and TIGIT are expressed on Tregs (125,139,141).…”

Section: Apc Tissuementioning

confidence: 99%

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Immune checkpoints in central nervous system autoimmunity

Joller

Peters

Anderson

et al. 2012

Immunological Reviews

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Summary A number of autoimmune diseases, including multiple sclerosis, are mediated by self-reactive T cells that have escaped the deletional mechanisms of central tolerance. Usually, these T cells are kept at bay through peripheral tolerance mechanisms including regulation through coinhibitory receptors and suppression by regulatory T cells (Tregs). However, if these mechanisms fail, self-reactive T cells are activated and autoimmune responses ensue. This review outlines how the coinhibitory receptors CTLA-4, PD-1, Tim-3 and TIGIT act at different checkpoints to inhibit autoreactive T cells and suppress the development of CNS autoimmunity. Loss of each of these receptors predisposes to autoimmunity, indicating a non-redundant role in maintaining peripheral tolerance. At the same time, their functional patterns seem to overlap to a large degree. We therefore propose that only the concerted action of a combination of inhibitory receptors is able to maintain peripheral tolerance and prevent autoimmunity.

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Section: Ctla‐4mentioning

confidence: 99%

Section: Functional Role Of Ctla-4 and Its Ligands In Cns Autoimmunitymentioning

confidence: 99%

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Immune checkpoints in central nervous system autoimmunity

Joller

Peters

Anderson

et al. 2012

Immunological Reviews

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“…(6) In addition, in vivo administration of the soluble fusion protein CTLA-4Ig, which interacts with both B7-1 and B7-2 and blocks their binding to mCD28 and mCTLA-4, (8) prevents the initiation of Th-mediated diseases, such as lupus, (9) collagen-induced arthritis, (10) and EAE. (11)(12)(13) Interferon-b1a/1b (IFN-b1a/1b) reduces the relapse rate in MS patients, as demonstrated by clinical and magnetic resonance imaging (MRI) parameters. (14) The mechanism of efficacy of IFN-b1a/1b in MS is poorly known, but there is evidence suggesting that it can affect the expression of costimulatory molecules involved in T cell activation.…”

mentioning

confidence: 99%

“…According to this hypothesis, sCTLA-4 was demonstrated to be effective in inhibiting the mixed leukocyte response in vitro, (6) and administration of sCTLA4Ig, a fusion protein able to antagonize mCD28/B7 binding, prevented T cell activation and initiation of EAE in vivo. (11)(12)(13) Inasmuch as CTLA-4Ig does not efficiently enter the central nervous system, a possible site of action of CTLA-4Ig could be brain microvascular endothelial cells (BMEC). These cells make up the structural basis of the blood-brain barrier (BBB) but can also express B7 molecules (22) and function as APC.…”

mentioning

confidence: 99%

IFN-β1a Modulates the Expression of CTLA-4 and CD28 Splice Variants in Human Mononuclear Cells: Induction of Soluble Isoforms

Giorelli

Livrea

Defazio

et al. 2001

Journal of Interferon & Cytokine Research

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Recently, mRNA encoding soluble isoforms of CD28 and CTLA-4 have been described in human lymphocytes. We demonstrate that interferon-beta1a (IFN-beta1a) can enhance the expression of these transcripts in human mononuclear cells. Because soluble CD28 and CTLA-4 molecules might affect T cell activation, our findings suggest an additional means whereby IFN-beta therapy might exert its immunomodulatory effects in multiple sclerosis (MS).

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CTLA-4 is required for the induction of high dose oral tolerance

Samoilova

Horton²,

Zhang³

et al. 1998

International Immunology

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Mucosal and systemic administrations of high dose antigens induce long-lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.

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CTLA4-Ig treatment prevents murine experimental autoimmune encephalomyelitis

Cited by 3 publications

References 0 publications

Immune checkpoints in central nervous system autoimmunity

Immune checkpoints in central nervous system autoimmunity

IFN-β1a Modulates the Expression of CTLA-4 and CD28 Splice Variants in Human Mononuclear Cells: Induction of Soluble Isoforms

CTLA-4 is required for the induction of high dose oral tolerance

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